Brain tumors are among the leading cause of death among young children and adults. A survey by the American Cancer Society has documented that 13,300 people died of brain tumors in 1995 and over 17,900 will die in 1996 (Parker et al., 1996, CA Cancer J. Clin., 46:5-28). The number of deaths due to brain tumors has been increasing at a significant rate each year. On average, 25,000 Americans are diagnosed with brain cancer yearly. Brain tumors claim the lives of more children than any other form of cancer except leukemia.
The increased incidence of brain tumors is not only evident in children but also in adults. It has been documented that a significant increase in mortality has occurred in adult primary malignant tumors between 1982 and 1996 (Parker et al., 1996, CA Cancer J. Clin., 46:5-28). Glioblastomas, astrocytomas an d meningiomas are the most common brain tumors that affect adults (Thapar and Laws, 1993, CA Cancer J. Clin., 43:263-271).
Glioblastoma multiforme are high grade astrocytomas that grow very rapidly and contain cells that are very malignant (Thapar and Laws, 1993, CA Cancer J. Clin., 43:263-271). The molecular basis of glioblastoma multiforme occurrence may involve systematic events at the chromosomal level or at a gene expression level. These may include inactivation of tumor suppressor genes, activation of oncogenes or specific translocations at the chromosomal level. Some genetic changes at the chromosomal level and gene expression level have been well documented for other brain tumors (Furnari et al., 1995, Cancer Surv., 25:233-275). For example, it has been documented that loss of tumor suppressor(s) genes at chromosome 10, mutations in p53, or overexpression of epidermal growth factor receptor, may be major events leading to glioblastoma multiforme. A number of other genes such as EGFR, CD44, .beta.4 integrins, membrane-type metalloproteinase (MT-MMP), p21, p16, p15, myc, and VEGF have been shown to be overexpressed in different types of brain tumors (Faillot et al., 1996 Neurosurgery, 39:478-483; Eibl et al., 1995, J. of Neurooncol., 26:165-170; Previtali et al., 1996, Neuropathol. Exp. Neurol. 55:456-465; Yamamoto et al., 1996, Cancer Res., 56:384-392; Jung et al., 1995, Oncogene, 11:2021-2028; Tsuzuki et al., 1996, Cancer, 78:287-293; Chen et al., 1995, Nature Med., 1:638-643; Takano, et al., 1996, Cancer Res., 56:2185-2190; Bogler et al., 1995, Glia, 15:308-327). Other genes such as p53 show mutations in the majority of brain tumors (Bogler et al., supra). How the interplay of one or more of these genes leads to tumorigenesis is not known but most likely multiple steps are required for neoplastic transformation. The exact series of events that lead to initiation or progression of glioblastoma are not known at present and useful markers for early detection of brain tumors are lacking.
Citation of references herein shall not be construed as an admission that such references are prior art to the present invention.